Age-related Changes of Nitric Oxide Synthase Isoforms and Endothelin-1 in Rat Corpus Cavernosum

Park, Bu Kyung; Oh, Geom Su; Park, Nam Cheol

Abstract

PURPOSE: Relaxation of the penile cavernous smooth muscle, which is the main process in penile erection, is controlled by endothelial-derived substances. This study was designed to determine whether aging resulted in altered endothelial autocrine/paracrine function.
MATERIALS AND METHODS
We analyzed the distribution of endothelin-1 (ET-1) and nitric oxide synthase (NOS) in the isolated corpus cavernosum from both young (12 weeks old) and aged (50 and 80 weeks old) rats by immunohistochemical (IHC) staining. Vascular mRNA expressions of NOS isoforms and ET-1 were also analyzed by reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS
The concentration of nitrite/nitrate in the corpus cavernosum was significantly decreased in aged rats but plasma nitrite/nitrate concentration was not changed by aging. IHC staining revealed that the aged vessels showed a marked IHC staining for inducible NOS (iNOS) although the vessels from 12-week-old rats were negative for iNOS. In contrast, there was a reduction of immunoreactivity for endothelial NOS (eNOS) with aging. With aging, expression of eNOS mRNA was slightly decreased in the corpus cavernosum. However, expression of iNOS mRNA was markedly increased with increasing age. IHC staining for vascular ET-1 peptide in young rats showed a scanty distribution in the endothelial cell layer. However, the staining for ET-1 increased both the endothelial cells and vascular smooth muscle layers in the aged rats. mRNA expression of ET-1 gene was upregulated in the aged rats.
CONCLUSIONS
It is suggested that the activation of vascular endothelin cascade and alterations in the expression of NOS isoforms may play an important role in the age-dependent, vasculogenic, erectile dysfunction.